Antioxidant compositions and use for treatment of hepatic steatosis and steatohepatitis

Abstract

A composition and method for treating hepatic steatosis, steatohepatitis, and liver diseases associated with or characterized by these conditions. The composition consists essentially of defined amounts of soluble vitamin E, mixed carotenoids and selenium and in one aspect, can include at least one additional agent for the treatment of these conditions.

What is claimed is:  
     
       1. A pharmaceutical composition for treatment of a patient who has hepatic steatosis or steatohepatitis, or who has at least one symptom associated with hepatic steatosis or steatohepatitis, said composition consisting essentially of: 
       a. soluble vitamin E in an amount of between about 10 international units per kilogram body weight of the patient per day (IU/kg/day) and about 20 IU/kg/day;  
       b. mixed carotenoids in an amount of between about 0.1 milligram per kilogram body weight of the patient per day (mg/kg/day) and about 1 mg/kg/day; and,  
       c. selenium in an amount of between about 0.5 microgram per kilogram body weight of the patient per day (μg/kg/day) and about 3 μg/kg/day.  
     
     
       2. The composition of  claim 1 , wherein said vitamin E is D-alpha tocopheryl polyethylene glycol-1000 succinate. 
     
     
       3. The composition of  claim 1 , wherein said mixed carotenoids comprise natural source water-dispersible β-carotene. 
     
     
       4. The composition of  claim 1 , wherein said selenium is sodium selenite pentahydrate. 
     
     
       5. The composition of  claim 1 , wherein said composition consists essentially of: 
       a. the soluble vitamin E in an amount of between about 10 IU/kg/day and about 20 IU/kg/day;  
       b. the mixed carotenoids in an amount of between about 0.2 mg/kg/day and about 0.5 mg/kg/day; and,  
       c. the selenium in an amount of between about 1 μg/kg/day and about 2 μg/kg/day.  
     
     
       6. The composition of  claim 1 , wherein said composition consists essentially of: 
       a. the soluble vitamin E at a concentration of from about 10 IU vitamin E per milliliter of the composition (10 IU/ml) to about 20 IU/ml;  
       b. the mixed carotenoids at a concentration from about 0.1 mg per ml of the composition (0.1 mg/ml) to about 0.75 mg/ml; andm,  
       c. the selenium at a concentration of from about 1 μg per ml of the composition (1 μg/ml) to about 5 μg/ml.  
     
     
       7. A pharmaceutical composition for treatment of a patient who has hepatic steatosis o steatohepatitis, or who has at least one symptom associated with hepatic steatosis or steatohepatitis, said composition comprising: 
       a. soluble vitamin E in an amount of between about 10 international units per kilogram body weight of the patient per day (IU/kg/day) and about 100 IU/kg/day;  
       b. mixed carotenoids in an amount of between about 0.1 milligram per kilogram body weight of the patient per day (mg/kg/day) and about 1 mg/kg/day;  
       c. selenium in an amount of between about 0.5 microgram per kilogram body weight of the patient per day (μg/kg/day) and about 3 μg/kg/day; and,  
       d. an agent selected from the group consisting of ursodeoxycholic add, tauro-ursodeoxycholic acid, and a derivative thereof selected from the group consisting of monosulfate and disulfate esters of ursodeoxycholic acid or tauro-ursodeoxycholic acid, derivatives thereof having increased solubility in water, and derivatives thereof that are useful for treating liver disease.  
     
     
       8. The composition of  claim 7 , wherein said composition consists essentially of: 
       a. the soluble vitamin E in an amount of between about 25 IU/kg/day and about 50 IU/kg/day;  
       b. the mixed carotenoids in an amount of between about 0.2 mg/kg/day and about 0.5 mg/kg/day;  
       c. the selenium in an amount of between about 1 μg/kg/day and about 2 μg/kg/day; and  
       d. the agent selected from the group consisting of ursodeoxycholic acid, tauro-ursodeoxycholic acid, and a derivative thereof selected from the group consisting of monosulfate and disulfate esters of ursodeoxycholic acid or tauro-ursodeoxycholic acid, derivatives thereof having increased solubility in water, and derivatives thereof that are useful for treating liver disease.  
     
     
       9. The composition of  claim 7 , wherein said agent is ursodeoxycholic acid. 
     
     
       10. The composition of  claim 7 , wherein said vitamin E is D-alpha tocopheryl polyethylene glycol-1000 succinate. 
     
     
       11. The composition of  claim 7 , wherein said mixed carotenoids comprise natural source water-dispersible β-carotene. 
     
     
       12. The composition of  claim 7 , wherein said selenium is sodium selenite pentahydrate. 
     
     
       13. The composition of  claim 7 , wherein said composition comprises: 
       a. the soluble vitamin E in an amount of between about 25 IU/kg/day and about 75 IU/kg/day;  
       b. the mixed carotenoids in an amount of between about 0.2 mg/kg/day and about 0.5 mg/kg/day;  
       c. the selenium in an amount of between about 1 μg/kg/day and about 2 μg/kg/day; and  
       d. the agent selected from the group consisting of ursodeoxycholic acid, tauro-ursodeoxycholic acid, and a derivative thereof selected from the group consisting of monosulfate and disulfate esters of ursodeoxycholic acid or tauro-ursodeoxycholic acid, derivatives thereof having increased solubility in water, and derivatives thereof that are useful For treating liver disease.  
     
     
       14. The composition of  claim 7 , wherein said vitamin E is water soluble. 
     
     
       15. A method of treating liver injury resulting from hepatic steatosis or steatohepatitis in a patient, said method comprising administering to a patient who has hepatic steatosis or steatohepatitis, or who has at least one symptom associated with said hepatic steatosis or steatohepatitis, a pharmaceutical composition consisting essentially of soluble Vitamin E, mixed carotenoids and selenium. 
     
     
       16. The method of  claim 15 , wherein said hepatic steatosis is nonalcoholic steatohepatitis. 
     
     
       17. The method of  claim 15 , wherein said composition consists essentially of; 
       a. the soluble vitamin E in an amount of between about 10 international units per kilogram body weight of the patient per day (IU/kg/day) and about 100 IU/kg/day;  
       b. the mixed carotenoids in an amount of between about 0.1 milligram per kilogram body weight of the patient per day (μg/kg/day) and about 1 mg/kg/day; and  
       c. the selenium in an amount of between about 0.5 microgram per kilogram body weight of the patient per day (mg/kg/day) and about 3 μg/kg/day.  
     
     
       18. The method of  claim 15 , wherein said vitamin E is D-alpha tocopheryl polyethylene glycol-1000 succinate. 
     
     
       19. The method of  claim 15 , wherein said mixed carotenoids comprise natural source water-dispersible β-carotene. 
     
     
       20. The method of  claim 15 , wherein said selenium is sodium selenite pentahydrate. 
     
     
       21. The method of  claim 15 , wherein said composition consists essentially of: 
       a. the soluble vitamin E in an amount of between about 25 IU/kg/day and about 75 IU/kg/day;  
       b. the mixed carotenoids in an amount of between about 0.2 mg/kg/day and about 0.5 mg/kg/day; and,  
       c. the selenium in an amount of between about 1 μg/kg/day and about 2 μg/kg/day.  
     
     
       22. The method of  claim 15 , wherein said composition consists essentially of: 
       a. the soluble vitamin E in an amount of between about 25 IU/kg/day and about 50 IU/kg/day;  
       b. the mixed carotenoids in an amount of between about 0.2 mg/kg/day and about 0.5 mg/kg/day; and,  
       c. the selenium, in an amount of between about 1 μg/kg/day and about 2 μg/kg/day.  
     
     
       23. The method of  claim 15 , wherein said composition consists essentially of: 
       a. the soluble vitamin E at a concentration of from about 20 IU vitamin E per milliliter of the composition (20 IU/ml) to about 75 IU/ml;  
       b. the mixed carotenoids at a concentration from about 0.1 mg per ml of the composition (01 mg/ml) to about 0.75 mg/ml; and,  
       c. the selenium at a concentration of from about 1 μg per ml of the composition (1 μg/ml) to about 5 μg/ml.  
     
     
       24. A method of treating liver injury resulting from hepatic steatosis or steatohepatitis in a patient, said method comprising administering to a patient who has hepatic steatosis or steatohepatitis, or who has at least one symptom associated with hepatic steatosis or steatohepatitis, a pharmaceutical composition comprising soluble Vitamin E, mixed carotenoids, selenium, and at least one additional agent for the treatment of liver injury resulting from hepatic steatosis or steatohepatitis, wherein said soluble vitamin E is administered in an amount of between about 10 international units per kilogram body weight of the patient per day (IU/kg/day) and about 100 IU/kg/day. 
     
     
       25. The method of  claim 24 , wherein said pharmaceutical composition comprises: 
       a. the soluble vitamin E in an amount of between about 10 international units per kilogram body weight of the patient per clay (IU/kg/day) and about 100 IU/kg/day;  
       b. the mixed carotenoids in an amount of between about 0.1 milligram per kilogram body eight of the patient per day (mg/kg/day) and about 1 mg/kg/day;  
       c. the selenium in an amount of between about 0.5 microgram per kilogram body weight of the patient per day (μg/kg/day) and about 3 μg/kg/day; and  
       d. the at least one additional agent for the treatment of liver injury resulting from hepatic steatosis or steatohepatitis.  
     
     
       26. The method of  claim 24 , wherein said agent for the treatment of hepatic steatosis or steatohepatitis is ursodeoxycholic acid, tauro-ursodeoxycholic acid or a derivative thereof selected from the group consisting of monosulfate and disulfate esters thereof, derivatives thereof having increased solubility in water, and deny that are useful for treating liver disease. 
     
     
       27. The method of  claim 24 , wherein said agent for the treatment of hepatic steatosis or steatohepatitis is ursodeoxycholic acid. 
     
     
       28. The method of  claim 24 , wherein said vitamin E is water soluble.